Colorectal CancerPhase 1/2NCT00819169

QUILT-3.026: AMG 655 in Combination With AMG 479 in Advanced, Refractory Solid Tumors

A Phase 1/2 study testing AMG 479 and AMG 655 in people with Colorectal Cancer and Locally Advanced, run by NantCell, Inc..

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

This is a multi-center, 2-part phase 1b/2 study of AMG 655 in combination with AMG 479 to be conducted in the United States and Spain. Part 1 is a dose escalation segment to identify a dose of AMG 655 in combination with AMG 479 that is safe and tolerable. Read more about this study

Who is it for?: Ages 16 years and older
Conditions the study is for: Colorectal Cancer, Locally Advanced, Metastatic Cancer
What is being tested?: AMG 479 and AMG 655
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 89 participants
Where: No sites listed yet
Study dates: 16 Jan 2009to 10 Aug 2011
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 16 years and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

Part 1: Histologically or cytologically confirmed, locally advanced or metastatic, treatment-refractory solid tumors
Part 2: Histologically or cytologically confirmed, locally advanced or metastatic: NSCLC (squamous or non-squamous cell carcinoma; up to 2 prior treatment regimens), Colorectal Cancer (up to 2 prior treatment regimens), Pancreatic Cancer (up to 1 prior treatment regimen), Ovarian cancer (up to 2 prior treatment regimens), or Sarcoma (up to 2 prior treatment regimens), according to cohort availability
Eastern Cooperative Group (ECOG performance status of 0 or 1
Women or men ≥16 years of age
Adequate hematology, renal, hepatic, coagulation and glycemic function.

Who cannot join

Presence of uncontrolled central nervous system (CNS) disease
Systemic chemotherapy, hormonal therapy, immunotherapy, experimental or approved anticancer proteins/antibodies therapy ≤28 days before enrollment.
Prior treatment with death receptor agonists (including but not limited to rhApo2L/TRAIL [AMG951], apomab, mapatumumab, lexatumumab, CS-1008)
Prior treatment with IGF receptor antagonists (including but not limited to CP-751, 871, MK0646, AVE1642 or IMC-A12)

About this study

Official title: A Phase 1b/2 Open Label, Dose Escalation Study of AMG 655 in Combination With AMG 479 in Subjects With Advanced, Refractory Solid Tumors

This is a multi-center, 2-part phase 1b/2 study of AMG 655 in combination with AMG 479 to be conducted in the United States and Spain.

Part 1 is a dose escalation segment to identify a dose of AMG 655 in combination with AMG 479 that is safe and tolerable.

Part 2 will evaluate the safety and estimate the efficacy of AMG 655 at the dose selected in Part 1 in combination with AMG 479 for the treatment of patients with advanced NSCLC (non-squamous histology; squamous histology), CRC, pancreatic cancer, ovarian cancer, and sarcoma.

Conditions: Colorectal Cancer, Locally Advanced, Metastatic Cancer, Non-Small Cell Lung Cancer, Ovarian Cancer, Pancreatic Cancer
Being tested: AMG 479, AMG 655
Keywords: AMG 655, AMG 479, Apoptosis, Monoclonal Antibody, Tumor Necrosis Factor, Insulin-like Growth Factor
Medical subject headings: Colorectal Neoplasms, Neoplasm Metastasis, Carcinoma, Non-Small-Cell Lung, Ovarian Neoplasms, Pancreatic Neoplasms, Sarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AMG 479Biological
AMG 479 is an investigational, fully human, monoclonal antibody that binds with Insulin-like growth factor receptor type 1.
AMG 655Biological
Also called AMG 655 is also known as conatumumab.
AMG 655 is an investigational, fully human, monoclonal antibody that binds with TNF-related apoptosis-inducing ligand, DR 5.

Study groups in NCT00819169
Study group	Role	What they receive
Part 1 Cohort 3	Experimental	AMG 479 18 mg/kg IV plus AMG 655 15 mg/kg IV (day 1 of each Q3W cycle) Receives: Biological: AMG 479; Biological: AMG 655
Part 1 Cohort 1	Experimental	AMG 479 18 mg/kg IV plus AMG 655 1 mg/kg IV (day 1 of each Q3W cycle) Receives: Biological: AMG 479; Biological: AMG 655
Part 1 Cohort 2	Experimental	AMG 479 18 mg/kg IV plus AMG 655 3 mg/kg IV (day 1 of each Q3W cycle) Receives: Biological: AMG 479; Biological: AMG 655
Part 2	Experimental	AMG 479 18 mg/kg IV plus AMG 655 15 mg/kg Q3W, or the MTD, as determined in Part 1 of the study Receives: Biological: AMG 479; Biological: AMG 655

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Dose-limiting Toxicities
Incidence of adverse events and clinical laboratory abnormalities defined as DLTs. Dose-limiting toxicities included any grade 3 or higher hematologic or nonhematologic toxicity related to conatumumab or the combination of conatumumab with ganitumab except for lymphocytopenia and anemia.
Measured: Time from first dose up to 24 months
Objective Response Rate
The objective response rate (ORR) is defined as confirmed complete response or partial response using modified Response Evaluation Criteria in Solid Tumors [RECIST]: a complete response is the disappearance of all target lesions; a partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Measured: Time from first dose up to 24 months

Secondary outcomes (6)

Progression Free Survival
Progression-free survival is defined as the number of days from study day 1 (first dose of investigational product) to the first observation of disease progression (by modified RECIST; or clinical progression, whichever came first) or death due to any cause. Disease progression by RECIST is defined as at least a 20% increase in the sum of diameters of target lesions in reference to the smallest sum on study and an absolute increase of at least 5 mm; the appearance of any new lesions is also considered progression.
Measured: Time from first dose up to 24 months
To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation
Measured: Time from first dose up to 24 months
To Evaluate the Concentration Level of AMG 655
Median, minimum, and maximum concentration of AMG 655 at specified time points.
Measured: Cycle 1 Day 1 end of infusion; Cycle 3 Day 1 end of infusion (each cycle is 28 days, each infusion is up to 1 hour)
To Evaluate the Concentration Level of AMG 479
Median, minimum, and maximum concentration of AMG 479 at specified time points.
Measured: Cycle 1 Day 1 end of infusion; Cycle 3 Day 1 end of infusion (each cycle is 28 days, each infusion is up to 1 hour)
Time to Response
Time to response is the time from study day 1 to the first observation of an objective response. Subjects without an objective response are excluded from the analysis of this endpoint. Objective response is defined as a tumor response assessment of either complete response or partial response per modified Response Evaluation Criteria in Solid Tumors (RECIST) and will be determined based on the Investigator-reported assessment only for subjects with measurable disease at baseline. Per RECIST v 1.1: a complete response is the disappearance of all target lesions; a partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Measured: Time from first dose up to 24 months
Duration of Response
Duration of response is defined as the number of days between the date of first objective response to the time of the first progressive disease (per modified Response Evaluation Criteria in Solid Tumors [RECIST] or clinical progression, whichever occurs first) or death due to any cause. Objective response is defined as a tumor response assessment of either complete response or partial response per modified RECIST where a complete response is the disappearance of all target lesions and a partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Per RECIST v 1.1, disease progression is defined as at least a 20% increase in the sum of diameters of target lesions in reference to the smallest sum on study and an absolute increase of at least 5 mm; the appearance of any new lesions is also considered progression.
Measured: Time from objective response to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

16 Jan 200910 Aug 2011

First posted8 Jan 2009 (estimated)
Study start16 Jan 2009
Primary completion10 Aug 2011
Study completion10 Aug 2011

Why it stopped: Sponsor decision - subjects rolled over to protocol 20101116

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Colorectal CancerStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 89 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00819169
Sponsor's protocol ID: 20070411
Other IDs: QUILT-3.026
Status last verified: Jul 2024
First submitted: 6 Jan 2009
Last updated: 20 Aug 2024
Results posted: Yes, on ClinicalTrials.gov

Publications

Tabernero J, Chawla SP, Kindler H, Reckamp K, Chiorean EG, Azad NS, Lockhart AC, Hsu CP, Baker NF, Galimi F, Beltran P, Baselga J. Anticancer activity of the type I insulin-like growth factor receptor antagonist, ganitumab, in combination with the death receptor 5 agonist, conatumumab. Target Oncol. 2015 Mar;10(1):65-76. doi: 10.1007/s11523-014-0315-z. Epub 2014 May 11.
PubMed 24816908

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Study at a glance

From the registry record, last updated by the sponsor on 20 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1b/2 Open Label, Dose Escalation Study of AMG 655 in Combination With AMG 479 in Subjects With Advanced, Refractory Solid Tumors
ClinicalTrials.gov ID: NCT00819169
Acronym / sponsor ID: 20070411
Conditions: Colorectal Cancer, Locally Advanced, Metastatic Cancer, Non-Small Cell Lung Cancer, Ovarian Cancer, Pancreatic Cancer
Keywords: AMG 655, AMG 479, Apoptosis, Monoclonal Antibody, Tumor Necrosis Factor, Insulin-like Growth Factor
Phase: Phase 1/2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Sponsor decision - subjects rolled over to protocol 20101116
Enrolment: 89 participants (actual)
Lead sponsor: NantCell, Inc.Industry (pharma, biotech, devices)
Study start: 16 Jan 2009 (actual)
Primary completion: 10 Aug 2011 (actual)
Study completion: 10 Aug 2011 (actual)
First posted: 8 Jan 2009 (estimated)
Results: Posted 20 Aug 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This is a multi-center, 2-part phase 1b/2 study of AMG 655 in combination with AMG 479 to be conducted in the United States and Spain.

Part 1 is a dose escalation segment to identify a dose of AMG 655 in combination with AMG 479 that is safe and tolerable.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
Part 1 Cohort 3	Experimental	Biological: AMG 479, Biological: AMG 655AMG 479 18 mg/kg IV plus AMG 655 15 mg/kg IV (day 1 of each Q3W cycle)
Part 1 Cohort 1	Experimental	Biological: AMG 479, Biological: AMG 655AMG 479 18 mg/kg IV plus AMG 655 1 mg/kg IV (day 1 of each Q3W cycle)
Part 1 Cohort 2	Experimental	Biological: AMG 479, Biological: AMG 655AMG 479 18 mg/kg IV plus AMG 655 3 mg/kg IV (day 1 of each Q3W cycle)
Part 2	Experimental	Biological: AMG 479, Biological: AMG 655AMG 479 18 mg/kg IV plus AMG 655 15 mg/kg Q3W, or the MTD, as determined in Part 1 of the study

Who may qualify

Ages: 16 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (5 listed)

Part 1: Histologically or cytologically confirmed, locally advanced or metastatic, treatment-refractory solid tumors
Part 2: Histologically or cytologically confirmed, locally advanced or metastatic: NSCLC (squamous or non-squamous cell carcinoma; up to 2 prior treatment regimens), Colorectal Cancer (up to 2 prior treatment regimens), Pancreatic Cancer (up to 1 prior treatment regimen), Ovarian cancer (up to 2 prior treatment regimens), or Sarcoma (up to 2 prior treatment regimens), according to cohort availability
Eastern Cooperative Group (ECOG performance status of 0 or 1
Women or men ≥16 years of age
Adequate hematology, renal, hepatic, coagulation and glycemic function.

Key exclusion criteria (4 listed)

Presence of uncontrolled central nervous system (CNS) disease
Systemic chemotherapy, hormonal therapy, immunotherapy, experimental or approved anticancer proteins/antibodies therapy ≤28 days before enrollment.
Prior treatment with death receptor agonists (including but not limited to rhApo2L/TRAIL [AMG951], apomab, mapatumumab, lexatumumab, CS-1008)
Prior treatment with IGF receptor antagonists (including but not limited to CP-751, 871, MK0646, AVE1642 or IMC-A12)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
AMG 479AMG 479 is an investigational, fully human, monoclonal antibody that binds with Insulin-like growth factor receptor type 1.	Biological	Part 1 Cohort 1, Part 1 Cohort 2, Part 1 Cohort 3, Part 2
AMG 655Also: AMG 655 is also known as conatumumab.AMG 655 is an investigational, fully human, monoclonal antibody that binds with TNF-related apoptosis-inducing ligand, DR 5.	Biological	Part 1 Cohort 1, Part 1 Cohort 2, Part 1 Cohort 3, Part 2

Primary outcome

Number of Participants With Dose-limiting Toxicities
Time frame: Time from first dose up to 24 months
Incidence of adverse events and clinical laboratory abnormalities defined as DLTs. Dose-limiting toxicities included any grade 3 or higher hematologic or nonhematologic toxicity related to conatumumab or the combination of conatumumab with ganitumab except for lymphocytopenia and anemia.
Objective Response Rate
Time frame: Time from first dose up to 24 months
The objective response rate (ORR) is defined as confirmed complete response or partial response using modified Response Evaluation Criteria in Solid Tumors [RECIST]: a complete response is the disappearance of all target lesions; a partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

6 secondary outcomes

Progression Free Survival
Time frame: Time from first dose up to 24 months
To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation
Time frame: Time from first dose up to 24 months
To Evaluate the Concentration Level of AMG 655
Time frame: Cycle 1 Day 1 end of infusion; Cycle 3 Day 1 end of infusion (each cycle is 28 days, each infusion is up to 1 hour)
To Evaluate the Concentration Level of AMG 479
Time frame: Cycle 1 Day 1 end of infusion; Cycle 3 Day 1 end of infusion (each cycle is 28 days, each infusion is up to 1 hour)
Time to Response
Time frame: Time from first dose up to 24 months
Duration of Response
Time frame: Time from objective response to 24 months

Results and safety

Results posted to the registry on 20 Aug 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part 1 Cohort 1	3	0
Part 1 Cohort 2	3	0
Part 1 Cohort 3	3	0
Part 2 Cohort 1	15	3
Part 2 Cohort 2	8	0
Part 2 Cohort 3	16	0
Part 2 Cohort 4	16	0
Part 2 Cohort 5	9	0
Part 2 Cohort 6	16	3

Primary outcome: Number of Participants With Dose-limiting Toxicities

Time frame: Time from first dose up to 24 months. Count of participants. Unit: Participants

Measure	Part 1 Cohort 1 n = 3	Part 1 Cohort 2 n = 3	Part 1 Cohort 3 n = 3
Value	0	0	0

Primary outcome: Objective Response Rate

Time frame: Time from first dose up to 24 months. Count of participants. Unit: Participants

Measure	Part 1 Cohort 1 n = 3	Part 1 Cohort 2 n = 3	Part 1 Cohort 3 n = 3	Part 2 Cohort 1 n = 15	Part 2 Cohort 2 n = 7	Part 2 Cohort 3 n = 16	Part 2 Cohort 4 n = 16	Part 2 Cohort 5 n = 9	Part 2 Cohort 6 n = 15
Value	1	0	0	0	0	0	0	0	0

Population analysed: A subject was included in the analysis if they received at least one dose of study drug.

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: All serious adverse events that occurred after the subject signed the informed consent form through to the Day 30 Safety Follow-up Visit or 30 days after the last dose of protocol-specified therapy, whichever was later, up to 25 months. All non-serious adverse events that occurred after enrollment through to the Day 30 Safety Follow-up Visit or 30 days after the last dose of protocol-specified therapy, whichever was later, up to 25 months.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part 1 Cohort 1	2 of 3 (66.7%)	3 of 3 (100%)	1 of 3
Part 1 Cohort 2	0 of 3 (0%)	3 of 3 (100%)	1 of 3
Part 1 Cohort 3	2 of 3 (66.7%)	3 of 3 (100%)	3 of 3
Part 2 Cohort 1	3 of 15 (20%)	15 of 15 (100%)	8 of 15
Part 2 Cohort 2	6 of 7 (85.7%)	7 of 7 (100%)	5 of 8
Part 2 Cohort 3	2 of 16 (12.5%)	15 of 16 (93.8%)	7 of 16
Part 2 Cohort 4	3 of 16 (18.8%)	14 of 16 (87.5%)	9 of 16
Part 2 Cohort 5	3 of 9 (33.3%)	9 of 9 (100%)	4 of 9
Part 2 Cohort 6	2 of 15 (13.3%)	11 of 15 (73.3%)	7 of 16

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 24816908Tabernero J, Chawla SP, Kindler H, Reckamp K, Chiorean EG, Azad NS, Lockhart AC, Hsu CP, Baker NF, Galimi F, Beltran P, Baselga J. Anticancer activity of the type I insulin-like growth factor receptor antagonist, ganitumab, in combination with the death receptor 5 agonist, conatumumab. Target Oncol. 2015 Mar;10(1):65-76. doi: 10.1007/s11523-014-0315-z. Epub 2014 May 11.
AmgenTrials clinical trials websiteLink provided by the sponsor.
Related InfoLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

MD study director

Amgen

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing AMG 479 and AMG 655 in people with Colorectal Cancer and Locally Advanced, run by NantCell, Inc..

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 20 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Dose-limiting Toxicities (time frame: Time from first dose up to 24 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00819169, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2024.